Hepatitis B virus (HBV) is a virus with a DNA genome, which belongs to the Hepadnaviridae family and causes acute and chronic hepatitis. Hepatitis B virus (HBV) is classified into eight genotypes having a difference of about 8% or more in the gene nucleotide sequence, or it is classified into four serotypes adw, adr, ayw and ayr) based on the two antigenic determinants (d/y and w/r) of hepatitis B surface antigen (HBsAg). About 3.5 hundred million people worldwide have chronic hepatitis B virus (HBV) infection, and particularly, in Korea and China, people with chronic hepatitis B virus infection reach about 5-8%, and hepatitis B virus (HBV) infection is the major cause of liver disease and liver cancer. Currently developed vaccines can be somewhat effective in the prevention of hepatitis B virus infection, but a significant number of patients with chronic infection with hepatitis B virus still exist. Chronic infection with hepatitis B virus (HBV) causes hepatitis, cirrhosis and liver cancer, and the incidence of liver cancer is about 300 times higher in people with chronic hepatitis B virus than in non-infected people. According to the WHO report, about 80% of liver cancer is caused by chronic hepatitis B.
Currently known therapeutic agents for hepatitis B include the nucleoside analogues including lamivudine and adefovir dipivoxil, which inhibit the DNA replication of hepatitis B virus (HBV) by inhibiting the reverse transcriptase of hepatitis B virus polymerase (HBV polymerase). However, when these drugs are administered for 3 years, drug-resistant virus occurs in about 75% of the patients to reduce the therapeutic effect of the drug. Due to this problem, it is impossible treat hepatitis B infection using the viral replication inhibitors alone. For this reason, it was attempted to use these inhibitors in combination with interferon agents, but these inhibitors are not currently used due to serious side effects.
For a similar purpose, a hepatitis B immune globulin (HBIG) preparation comprising a hepatitis B virus (HBV) antibody isolated from blood having a high antibody titer was considered. However, because the antibody of the HBIG preparation is isolated and purified from plasma, there are problems, including difficulty in obtaining plasma, the possibility of viral infection, low activity, high costs and the like.
In recent years, there have been reports of mutant viruses capable of avoiding such antibodies, for example, a mutant having a glycine-to-arginine substitution at position 145 of the surface protein of hepatitis B virus (HBV). In addition, various mutants capable of avoiding the antibodies have appeared. For this reason, it is difficult for the conventional hepatitis B virus therapeutic agents to show satisfactory therapeutic effects.
Thus, there is an urgent need to develop an antibody for treating hepatitis B virus (HBV), which binds specifically to a hepatitis B virus (HBV) epitope in which no mutation occurs, so that the therapeutic effect of the antibody is not reduced by the mutation.